Gonorrhea is a well known, sexually transmitted disease which produces acute suppuration of the mucous membranes of the genital urinary tract and the eye followed by chronic inflammation and fibrosis. It is caused by a gram negative group of cocci Neisseria gonorrhoeae (gonococcus). A single strain of this species is an isolate from a single host (patient) at a particular site. There are, therefore, multitudinous strains of N. gonorrhoeae, each of which has characteristic antigenic determinants assocated with the pili, a fact which renders both diagnosis and immunization difficult. The incidence of the disease has markedly increased since 1955, and has been complicated by the appearance of penicillin resistant strains harboring .beta.-lactamase encoding plasmids, which were first reported in 1976. The infectivity of the organism is extremely high, and it has been estimated that a single sexual encounter with an infected partner results in a 20-30% probability of acquiring the disease. If left untreated, relapses are to be expected, as resistance to re-infection does not appear to develop.
The course of the disease involves colonization of the mucous membranes by the bacterium, a process which is mediated by the attachment of the colonizing cell to the surface membrane by means of filamentous structures called pili associated with its cell wall. After attachment, the gonococcus is passed through the epithelium to the submucosal space where it is capable of causing inflammation and fibrosis. The attachment of the gonococci to the epithelial surface can be blocked by anti-pilus antibody.
In addition to blocking cell attachment, antibodies raised against pilus protein are also opsonic--i.e., they mediate the killing of the invading bacteria by the phagocytes in the blood. However, the use of pilus immunogens as vaccines has been rendered impractical by the lack of cross-reactivity among strains.
The lack of cross-reactivity of antibodies raised against pili of various strains has been shown not to be absolute. (Brinton, C. C. Jr. et al, Immunobiology of Neisseria Gonorrheae (1978) American Society for Microbiology, Washington, D.C., p. 155). Also, the nature of the pilus protein has been studied. The filamentous portion consists of a polymeric form of a monomeric polypeptide, pilin, and the complete amino acid sequence of the pilin isolated from the transparent colonial variant (Tr) of strain MS11 and a partial sequence of R10 (Tr) pilin have been determined (Schoolnik, G. K. et al, J. Exp. Med. (1984) 159:1351). It has also been shown that when the pilin associated with either of these two strains is treated with cyanogen bromide, two immunologically important fragments CNBr-2, residues 9-92, and CNBr-3, residues 93-159, are generated which appear to represent immunologically different portions of the molecule. CNBr-3 is apparently antigenically variable and immunodominant; CNBr-2 apparently contains a conserved receptor-binding region and is immunorecessive. (Schoolnik, G. K. et al, Prog. Allergy (1983) 33:314). None of the foregoing work has resulted in a material which can serve as a effective vaccine against all strains of N. gonorrhoeae. By providing an immunogenic form of an antigenic determinant capable of eliciting antibodies reactive against all strains either by inhibiting attachment, or by encouraging phagocytosis or both, protection would be provided against gonnorheal infection. This is the accomplishment of the present invention.